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Induction of specific-locus and dominant lethal mutations in male mice by ifosfamide (Holoxan)

Published online by Cambridge University Press:  01 December 1998

U. H. EHLING ,
J. FAVOR ,
A. NEUHÄUSER-KLAUS  and
I.-D. ADLER
U. H. EHLING
Affiliation:
GSF-National Research Centre for Environment and Health, Institute of Mammalian Genetics, Ingolstaedter Landstrasse, D-85764 Neuherberg, Germany
J. FAVOR
Affiliation:
GSF-National Research Centre for Environment and Health, Institute of Mammalian Genetics, Ingolstaedter Landstrasse, D-85764 Neuherberg, Germany
A. NEUHÄUSER-KLAUS
Affiliation:
GSF-National Research Centre for Environment and Health, Institute of Mammalian Genetics, Ingolstaedter Landstrasse, D-85764 Neuherberg, Germany
I.-D. ADLER
Affiliation:
GSF-National Research Centre for Environment and Health, Institute of Mammalian Genetics, Ingolstaedter Landstrasse, D-85764 Neuherberg, Germany
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Abstract

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Ifosfamide induced dominant lethal mutations in spermatozoa of mice at doses of 200 and 300 mg/kg and in spermatids and spermatocytes at 600 mg/kg. The highest dose also induced specific-locus mutations in post-spermatogonial germ-cell stages of mice but not in spermatogonial stem cells. The nature of the induced mutations suggests they are intergenic. The spermatogenic specificity of ifosfamide in mouse germ cells is similar to that of the structurally related cytostatic drugs cyclophosphamide and trofosfamide. Due to the post-spermatogonial germ cell specificity of ifosfamide, the genetic risk is limited to a few weeks after exposure.

Type
Research Article
Information
Genetics Research , Volume 72 , Issue 3 , December 1998 , pp. 177 - 183
Copyright
© 1998 Cambridge University Press

Footnotes

This paper is dedicated to our friend and colleague Bruce Cattanach on the occasion of his retirement.